Targeted Delivery of Therapeutic Oligonucleotides for the Treatment of Prostate Cancer

摘要

Androgen independence and chemoresistance are the major obstacles in the treatment of patients with advanced prostate cancer (Denis & Murphy, 1993; Oh & Kantoff, 1998). Recent studies have suggested that overexpression of a proto-oncorprotein, Bcl-2, plays an important role in the development of androgen independence and chemoresistance in prostate cancer. We propose in this application to develop a tumor-specific vehicle to selectively deliver to the tumor an antisense oligodeoxynucleotides (ODN) that is targeted to Bcl-2. Down- regulation of Bcl-2 in prostate cancer could render it more susceptible to the standard chemotherapy. Sigma receptor will be chosen as the target as they are overexpressed in a number of tumors including prostate cancer.